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the last step of abatch manufacturing process and has no impact on the quality of
the batch for which the cleaning is performed.” Rather, itisthe first step in the
manufacture ofthe next product batch and can greatly impact the safety and
efficacy. Ifthe process owner, validation department, and, above all, the cleaning
operators view cleaning as the first step of manufacturing, the importance of a
properly designed, validated, and followed cleaning procedure is obvious. By
comparison, Tunner recognizes that “The effectiveness of an automated cleaning
process depends primarily on the equipment and program design, which is
confirmed by proper validation and maintained by an effective maintenance
program. Operator training, while important, is secondary to the process and
equipment design.”
In today’s manufacturing processes, Roebers (3) suggests that there is a
mandate to apply automated CIP, noting that “If you cannot clean your process
equipment and piping in a robust, reproducible way, don’t even think about
making abiopharmaceutical product!”
WHAT IS CIP?
Seiberling
The acronym CIP refers to acomplex technology that embraces: ( i )processing
equipment designed and fabricated to be CIPable, i.e., capable of being cleaned in
place, ( ii) permanently installed spray devices to the maximum extent possible,
( iii) CIP supply (CIPS)/return piping (CIPR), ( iv) aCIP skid with chemical feed
equipment, and ( v )acontrol system to run the CIP skid and deliver the cleaning
solutions in the correct sequences at the required composition, temperature,
pressure, and flow rate. The process control system must operate process equipment
pumps, valves, and other appurtenances to ensure the efficacy of the CIP
process. When applied to biopharmaceutical processes the general application is to
clean the process equipment and piping, generally in sequence, following each
period of use.
The train may be comprised of individual tanks or equipment items, or
groups of different sized tanks of similar function in series, the common element of
the CIP process being the transfer line from the first tank to the next. SIP logically
follows CIP,and the design of aCIPable process fulfills the major needs for SIP also,
via the addition of clean steam (CS) and condensate drain connections.
Components of aGeneric CIPable Process
Figure 1 illustrates a typical two-tank train supported by the requisite CIP
equipment and piping. The train could extend to include multiple systems to the
maximum extent possible in the applicable CIP circuits.The train may be individual
vessels in sequence, per this example, or several in parallel in sequence with others
in parallel via multiport transfer panels (TPs). The major components are identified
by number in Figure 1and include the following.
Vessels
Tanks T1 and T2, (1) each fitted with permanently installed fixed spray devices, a
vent filter, manway, agitator, and (not shown) a rupture disk or equivalent
overpressure protection device for the American Society of Mechanical Engineers
(ASME) code vessel. The vessel may include heat transfer surface in one or more
zones, and is commonly insulated for process and sterilize-in-place (SIP) reasons.